Study On Chemical Structure,Chain Conformation And Anti-inflammatory Activity Of Polysaccharide Degraded By Ultrasound

Objective: To investigate the chemical structure,chain structure and therapeutic effect of a novel sulfurated α-L-fucooligosaccharide(Fuc-S) prepared by ultrasonic degradation of Fucoidan and its therapeutic effect on inflammatory bowel disease(IBD).Methods: The molecular weight,radius of gyration and polydispersity of Fuc-S were studied by hpsec-malls;The monosaccharide composition of Fuc-S was determined by GC;The characteristic functional groups of Fuc-S were determined by FT-IR;The structure of Fuc-S was confirmed by NMR.Finally,the conformation of Fuc-S was determined according to various characterization methods,and its structure diagram was drawn.Then,Fuc-S was applied to C57 mice with chronic colitis induced by 1.8% dextran sodium sulfate(DSS) to verify its anti-inflammatory effect.The weight change and fecal occult blood of mice were recorded during the animal experiment,and the colon length of mice was measured.The disease activity index(DAI),hematoxylin and eosin(H&E) staining and immunofluorescence(IF)staining were used to evaluate the histopathology.Enzyme linked immunosorbent assay(ELISA) was used to analyze the levels of inflammatory factors in each experimental group.Western blotting(WB) was used to evaluate the differences in the expression levels of inflammatory proteins.RNA sequencing was used to explore the effect of Fuc-S on the changes of intestinal flora in mice.Results: The results showed that the molecular weight of the degraded fucoidan was lower and more uniform without changing the primary structure,and it also showed a stronger advantage in antiinflammatory biological activity.Fuc-S can effectively reduce the weight loss,colon shortening and DAI score increase induced by DSS in mice,and improve the symptoms of fecal occult blood.It improved the infiltration of inflammatory cells,the formation of lesions and the destruction of crypts,and decreased the expression of inflammatory factors and proteins.By inhibiting the richness of pathogenic Enterobacteriaceae,increasing the richness of beneficial Enterobacteriaceae and regulating tryptophan,we can improve the intestinal microbial imbalance caused by DSS.It was found that the anti-inflammatory activity of Fuc-S was at least partly mediated by the inactivation of PI3K/Akt and MAPKs signaling pathways.Conclusion: ultrasonic degradation of polysaccharides is a potential method to improve the physicochemical properties of polysaccharides.Fuc-S may be an effective functional food and drug for the prevention and treatment of IBD.Its mechanism is mainly through inhibiting PI3K/Akt and MAPKs pathway activation,inhibiting host tryptophan metabolism and regulating intestinal microbiota to inhibit inflammatory cell infiltration and pro-inflammatory cytokine production.